Prolyl hydroxylase mediated inhibition of fatty acid synthase to combat tumor growth in mammary gland carcinoma

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• 作者：Manjari Singh ; Uma Devi ; Subhadeep Roy ; Pushpraj S. Gupta…
• 关键词：Fatty acid synthase ; Hypoxia inducible factor ; Hypoxia ; Normoxia ; Prolyl hydoxylase
• 刊名：Breast Cancer
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：23
• 期：6
• 页码：820-829
• 全文大小：1,191 KB
• 刊物主题：Surgical Oncology; Oncology; Surgery; Cancer Research;
• 出版者：Springer Japan
• ISSN：1880-4233
• 卷排序：23

文摘

Cancer is a group of cells which grow in an uncontrolled manner and invades to the adjacent organs to form malignant tumors. Tumor hypoxia results due to contrast between the cellular oxygen expenditure and oxygen supply to the cells. Hypoxia inducible factor (HIF) is a heterodimeric transcription factor encompass of oxygen sensitive α subunit and constitutively expressed β subunit both of which are basic helix-loop-helix protein. The stability of HIF is primarily regulated by post translational prolyl hydroxylation, catalyzed by prolyl hydroxylase 2 (Phd-2). Phd-2 is a group of enzymes that acts as an oxygen sensor. Cancer cells have altered metabolism as they fulfil their energy needs through glycolysis and lipid biogenesis. HIF-1α is known to upregulate glycolysis by activating the transcription of enzymes on the glycolytic pathway and through lipogenesis. Cancer cells have over expressed fatty acid synthase owing to altered glycolytic pathway. Considering the above, it is hypothesized that chemical activation of Phd-2 can curtail down HIF-1α and subsequently fatty acid synthase expression.